16-67239406-T-G

Variant names:

• chr16-67239406-T-G
• NM_013241.3:c.250A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013241.3(FHOD1):​c.250A>C​(p.Thr84Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FHOD1 NM_013241.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

Genes affected

FHOD1 (HGNC:17905): (formin homology 2 domain containing 1) This gene encodes a protein which is a member of the formin/diaphanous family of proteins. The gene is ubiquitously expressed but is found in abundance in the spleen. The encoded protein has sequence homology to diaphanous and formin proteins within the Formin Homology (FH)1 and FH2 domains. It also contains a coiled-coil domain, a collagen-like domain, two nuclear localization signals, and several potential PKC and PKA phosphorylation sites. It is a predominantly cytoplasmic protein and is expressed in a variety of human cell lines. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

SLC9A5 (HGNC:11078): (solute carrier family 9 member A5) Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Implicated in end stage renal disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08802548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHOD1	NM_013241.3	c.250A>C	p.Thr84Pro	missense_variant	Exon 2 of 22	ENST00000258201.9	NP_037373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHOD1	ENST00000258201.9	c.250A>C	p.Thr84Pro	missense_variant	Exon 2 of 22	1	NM_013241.3	ENSP00000258201.4
SLC9A5	ENST00000564704.5	n.774+950T>G		intron_variant	Intron 1 of 15	1
FHOD1	ENST00000561922.1	n.250A>C		non_coding_transcript_exon_variant	Exon 2 of 13	2		ENSP00000458085.1
FHOD1	ENST00000567752.5	n.304A>C		non_coding_transcript_exon_variant	Exon 2 of 20	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.038
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.2	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.037
Sift	Benign	0.18	T
Sift4G	Benign	0.21	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.25		Gain of disorder (P = 0.0442);
MVP		0.39
MPC		0.86
ClinPred		0.27	T
GERP RS		2.7
Varity_R		0.17
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-67273309;